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Reconciling Flux Experiments for Quantitative Modeling of Normal and Malignant Hematopoietic Stem/Progenitor Dynamics

Takahashi, Munetomo ; Barile, Melania ; Chapple, Richard H. ; Tseng, Yu jung ; Nakada, Daisuke ; Busch, Katrin ; Fanti, Ann Kathrin ; Säwén, Petter LU ; Bryder, David LU and Höfer, Thomas , et al. (2021) In Stem Cell Reports 16(4). p.741-753
Abstract

Hematopoiesis serves as a paradigm for how homeostasis is maintained within hierarchically organized cell populations. However, important questions remain as to the contribution of hematopoietic stem cells (HSCs) toward maintaining steady state hematopoiesis. A number of in vivo lineage labeling and propagation studies have given rise to contradictory interpretations, leaving key properties of stem cell function unresolved. Using processed flow cytometry data coupled with a biology-driven modeling approach, we show that in vivo flux experiments that come from different laboratories can all be reconciled into a single unifying model, even though they had previously been interpreted as being contradictory. We infer from comparative... (More)

Hematopoiesis serves as a paradigm for how homeostasis is maintained within hierarchically organized cell populations. However, important questions remain as to the contribution of hematopoietic stem cells (HSCs) toward maintaining steady state hematopoiesis. A number of in vivo lineage labeling and propagation studies have given rise to contradictory interpretations, leaving key properties of stem cell function unresolved. Using processed flow cytometry data coupled with a biology-driven modeling approach, we show that in vivo flux experiments that come from different laboratories can all be reconciled into a single unifying model, even though they had previously been interpreted as being contradictory. We infer from comparative analysis that different transgenic models display distinct labeling efficiencies across a heterogeneous HSC pool, which we validate by marker gene expression associated with HSC function. Finally, we show how the unified model of HSC differentiation can be used to simulate clonal expansion in the early stages of leukemogenesis.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cell behaviour, cell dynamics, fate mapping, hematopoietic stem cells, kinetics, mathematical modeling, reconcile different published data
in
Stem Cell Reports
volume
16
issue
4
pages
13 pages
publisher
Cell Press
external identifiers
  • scopus:85103965487
  • pmid:33770496
ISSN
2213-6711
DOI
10.1016/j.stemcr.2021.02.020
language
English
LU publication?
yes
id
394ad4e0-e24b-48d9-b3fc-017678943e4a
date added to LUP
2021-04-20 12:16:29
date last changed
2022-08-04 08:41:42
@article{394ad4e0-e24b-48d9-b3fc-017678943e4a,
  abstract     = {{<p>Hematopoiesis serves as a paradigm for how homeostasis is maintained within hierarchically organized cell populations. However, important questions remain as to the contribution of hematopoietic stem cells (HSCs) toward maintaining steady state hematopoiesis. A number of in vivo lineage labeling and propagation studies have given rise to contradictory interpretations, leaving key properties of stem cell function unresolved. Using processed flow cytometry data coupled with a biology-driven modeling approach, we show that in vivo flux experiments that come from different laboratories can all be reconciled into a single unifying model, even though they had previously been interpreted as being contradictory. We infer from comparative analysis that different transgenic models display distinct labeling efficiencies across a heterogeneous HSC pool, which we validate by marker gene expression associated with HSC function. Finally, we show how the unified model of HSC differentiation can be used to simulate clonal expansion in the early stages of leukemogenesis.</p>}},
  author       = {{Takahashi, Munetomo and Barile, Melania and Chapple, Richard H. and Tseng, Yu jung and Nakada, Daisuke and Busch, Katrin and Fanti, Ann Kathrin and Säwén, Petter and Bryder, David and Höfer, Thomas and Göttgens, Berthold}},
  issn         = {{2213-6711}},
  keywords     = {{cell behaviour; cell dynamics; fate mapping; hematopoietic stem cells; kinetics; mathematical modeling; reconcile different published data}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{741--753}},
  publisher    = {{Cell Press}},
  series       = {{Stem Cell Reports}},
  title        = {{Reconciling Flux Experiments for Quantitative Modeling of Normal and Malignant Hematopoietic Stem/Progenitor Dynamics}},
  url          = {{http://dx.doi.org/10.1016/j.stemcr.2021.02.020}},
  doi          = {{10.1016/j.stemcr.2021.02.020}},
  volume       = {{16}},
  year         = {{2021}},
}